Effects of normal and high circulating concentrations of activin A on vascular endothelial cell functions and vasoactive factor production

- Physiological activin A concentrations observed during a normal pregnancy increased vascular endothelial proliferation and migration.
- Pathological pre-eclamptic concentrations increased vascular endothelial permeability, reduced proliferation and migration, and caused an imbalance in production of vasoactive factors.
- Activin A at pre-eclamptic concentrations may contribute to the systemic maternal vascular endothelial dysfunction observed in the disorder.

ObjectivesActivin A, a TGFβ family member, circulates in the maternal blood at increasing concentrations throughout gestation during a healthy pregnancy. The circulating concentration of activin A is further increased in pre-eclampsia (PE), a hypertensive disorder of pregnancy that is marked by systemic maternal vascular endothelial cell dysfunction. The effect of increasing activin A concentrations on the maternal vascular endothelium is unknown. The study aim was to investigate the effect of physiological and pathological activin A concentrations observed in normotensive and PE pregnancies respectively, on vascular endothelial cell function.Methods and resultsImmunostaining demonstrated the presence of the activin A receptor, ACVR2A, in SGHEC-7 cells used to model the vascular endothelium. SGHEC-7 cells were treated with activin A concentrations representative of concentrations throughout gestation in normotensive (0-10 ng/ml) and PE (50 ng/ml) pregnancies. xCELLigence functional assays revealed that normotensive activin A concentrations increased SGHEC-7 proliferation and migration, which was inhibited by PE concentrations. Additionally, fluorescence based assays showed that PE concentrations increased endothelial permeability. None of the tested activin A concentrations affected cell apoptosis. PE concentrations also resulted in an imbalance of the vasoactive factors eNOS, PTGIS and EDN1, as determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays.ConclusionCompared with normotensive activin A concentrations, the higher PE activin A concentrations resulted in abnormal endothelial functions, which may contribute to the systemic maternal vascular endothelial cell dysfunction observed in the disorder.